Pyrazoles have been widely described as pharmaceutical therapeutic agents, including antiinflammatories, and antidiabetic agents, among others. More recently, 3-haloalkyl-1H-pyrazole-1-yl!benzenesulfonamide have been identified as potent antiinflammatories without the side effects commonly-associated with such antiinflammatory agents. It became apparent that there was no known method to prepare such compounds, especially in a commercially viable one-pot synthesis incorporating common starting materials and reagents.
The formation of halogenated 1-aryl-butane-1,3-diones has been described K. Joshi et al., Pharmazie, 34, 68-9 (1979); K. Joshi et al., J. Ind. Chem. Soc., 60, 1074-6 (1983); R. Yo and S. Livingstone, Aust. J. Chem., 21, 1781-7 (1968); CA 2,041,134, ZA 7,104,221 and DE 2,429,674!.
In addition, the preparation of pyrazoles from the condensation of diketones and hydrazines has been described EP 418,845, EP 554,829, T. Nishiwaki, Bull. Chem. Soc. Japan, 42, 3024-26 (1969); J. Wright et al., J. Med. Chem., 7, 102-5 (1963); and R. Soliman and H. Feid-Allah, J. Pharm. Sci., 70, 602-5 (1980)!.
However, these preparations do not provide a scaleable commercial process. In addition, they require isolation of the intermediate diketone, which adds to the cost and complexity of the synthesis.